@article{3160406,
    title = "Polymorphisms of Helicobacter pylori signaling pathway genes and gastric
cancer risk in the European Prospective Investigation into
Cancer-Eurgast cohort",
    author = "Companioni, Osmel and Bonet, Catalina and Munoz, Xavier and Weiderpass, and Elisabete and Panico, Salvatore and Tumino, Rosario and Palli, Domenico and and Agnoli, Claudia and Vineis, Paolo and Boutron-Ruault, and Marie-Christine and Racine, Antoine and Clavel-Chapelon, Francoise and and Travis, Ruth C. and Khaw, Kay-Tee and Riboli, Elio and Murphy, Neil and and Vergnaud, Anne-Claire and Trichopoulou, Antonia and Benetou, Vassiliki and and Trichopoulos, Dimitrios and Lund, Eiliv and Johansen, Dorthe and and Lindkvist, Bjoern and Johansson, Mattias and Sund, Malin and Ardanaz, and Eva and Sanchez-Cantalejo, Emilio and Huerta, Jose M. and Dorronsoro, and Miren and Ramon Quiros, Jose and Tjonneland, Anne and Mortensen, Lotte and Maxild and Overvad, Kim and Chang-Claude, Jenny and Rizzato, Cosmeri and and Boeing, Heiner and De Mesquita, H. Bas Bueno and Siersema, Peter and and Peeters, Petra H. M. and Numans, Mattijs E. and Carneiro, Fatima and and Licaj, Idlir and Freisling, Heinz and Sala, Nuria and Gonzalez, Carlos and A.",
    journal = "International Journal  of Cancer",
    year = "2014",
    volume = "134",
    number = "1",
    pages = "92-101",
    publisher = "Wiley",
    issn = "0020-7136",
    doi = "10.1002/ijc.28357",
    keywords = "gastric cancer; genetic susceptibility; Helicobacter pylori; NOD2; CD14",
    abstract = "Helicobacter pylori is a recognized causal factor of noncardia gastric
cancer (GC). Lipopolysaccharide and peptidoglycan of this bacterium are
recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates
the transcription of pro-inflammatory cytokines to elicit an immune
response. Single nucleotide polymorphisms (SNPs) in these genes have
been associated with GC in different populations. We genotyped 30 SNPs
of these genes, in 365 gastric adenocarcinomas and 1,284 matched
controls from the European Prospective Investigation into Cancer cohort.
The association with GC and its histological and anatomical subtypes was
analyzed by logistic regression and corrected for multiple comparisons.
Using a log-additive model, we found a significant association between
SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the
multiple comparisons tests only the NOD2 region remained significant
(p=0.009). Analysis according to anatomical subtypes revealed NOD2 and
NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with
cardia GC, while analysis according to histological subtypes showed that
CD14 was associated with intestinal but not diffuse GC. The multiple
comparisons tests confirmed the association of NOD2 with noncardia GC
(p=0.0003) and CD14 with cardia GC (p=0.01). Haplotype analysis was in
agreement with single SNP results for NOD2 and CD14 genes. From these
results, we conclude that genetic variation in NOD2 associates with
noncardia GC while variation in CD14 is associated with cardia GC.
What’s new? Variations in immune genes appear to play an important role
in determining susceptibility to gastric cancer linked to Helicobacter
pylori colonization of gastric mucosa. However, little is known about
the influence of variation on anatomical localization and histological
subtype of this malignancy. The results of this study first confirm that
NOD2 and CD14, which encode proteins that recognize H. pylori
lipopolysaccharide and peptidoglycan, are significantly associated with
gastric cancer risk and second indicate that NOD2 associates with
noncardia and CD14 with cardia gastric cancer. The differential effects
of variation on the anatomical localization of disease warrant further
investigation."
}